Celastrol regulates psoriatic inflammation and autophagy by targeting IL-17A
Anti-IL-17A antibodies, such as secukinumab and ixekizumab, are effective proinflammatory cytokine inhibitors for autoimmune disorders, including psoriasis. However, anti-IL-17A small molecule treatments are yet to be commercialized. Celastrol, a natural compound extracted from the roots of traditio...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-03-01
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| Series: | Biomedicine & Pharmacotherapy |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0753332224001379 |
| _version_ | 1797291832258854912 |
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| author | Aeri Park Tae-Hwe Heo |
| author_facet | Aeri Park Tae-Hwe Heo |
| author_sort | Aeri Park |
| collection | DOAJ |
| description | Anti-IL-17A antibodies, such as secukinumab and ixekizumab, are effective proinflammatory cytokine inhibitors for autoimmune disorders, including psoriasis. However, anti-IL-17A small molecule treatments are yet to be commercialized. Celastrol, a natural compound extracted from the roots of traditional Chinese medicinal plants, has anti-inflammatory and antioxidant properties. However, the binding of celastrol to IL-17A and the associated anti-inflammatory mechanisms remain unclear. This study investigated whether celastrol could directly bind to IL-17A and regulate inflammation in psoriatic in vitro and in vivo models. The results showed that celastrol directly binds to IL-17A and inhibits its downstream signaling, including the NF-kB and MAPK pathways. Interestingly, celastrol restored autophagy dysfunction and reduced proinflammatory cytokine secretion in keratinocytes. In addition, celastrol increased autophagy in the epidermis of a mouse model of psoriasis. Celastrol decreased Th17 cell populations and proinflammatory cytokine levels in mice. Thus, IL-17A-targeting celastrol reduced inflammation by rescuing impaired autophagy in in vitro and in vivo models of psoriasis, demonstrating its potential as a substitute for anti-IL-17A antibodies for treating psoriasis. |
| first_indexed | 2024-03-07T19:42:30Z |
| format | Article |
| id | doaj.art-694ff1d5ea2347f094a580e5bf588203 |
| institution | Directory Open Access Journal |
| issn | 0753-3322 |
| language | English |
| last_indexed | 2024-03-07T19:42:30Z |
| publishDate | 2024-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Biomedicine & Pharmacotherapy |
| spelling | doaj.art-694ff1d5ea2347f094a580e5bf5882032024-02-29T05:17:55ZengElsevierBiomedicine & Pharmacotherapy0753-33222024-03-01172116256Celastrol regulates psoriatic inflammation and autophagy by targeting IL-17AAeri Park0Tae-Hwe Heo1Laboratory of PharmacoImmunology, Integrated Research Institute of Pharmaceutical Sciences and BK21 FOUR Team for Advanced Program for SmartPharma Leaders, College of Pharmacy, The Catholic University of Korea, 43 Jibong-ro, Bucheon-si, Gyeonggi-do 14662, Republic of KoreaCorrespondence to: NP512, Hall of Cardinal Jin-Suk Cheong, The Catholic University of Korea, 43 Jibong-ro, Bucheon-si, Gyeonggi-do 14662, South Korea.; Laboratory of PharmacoImmunology, Integrated Research Institute of Pharmaceutical Sciences and BK21 FOUR Team for Advanced Program for SmartPharma Leaders, College of Pharmacy, The Catholic University of Korea, 43 Jibong-ro, Bucheon-si, Gyeonggi-do 14662, Republic of KoreaAnti-IL-17A antibodies, such as secukinumab and ixekizumab, are effective proinflammatory cytokine inhibitors for autoimmune disorders, including psoriasis. However, anti-IL-17A small molecule treatments are yet to be commercialized. Celastrol, a natural compound extracted from the roots of traditional Chinese medicinal plants, has anti-inflammatory and antioxidant properties. However, the binding of celastrol to IL-17A and the associated anti-inflammatory mechanisms remain unclear. This study investigated whether celastrol could directly bind to IL-17A and regulate inflammation in psoriatic in vitro and in vivo models. The results showed that celastrol directly binds to IL-17A and inhibits its downstream signaling, including the NF-kB and MAPK pathways. Interestingly, celastrol restored autophagy dysfunction and reduced proinflammatory cytokine secretion in keratinocytes. In addition, celastrol increased autophagy in the epidermis of a mouse model of psoriasis. Celastrol decreased Th17 cell populations and proinflammatory cytokine levels in mice. Thus, IL-17A-targeting celastrol reduced inflammation by rescuing impaired autophagy in in vitro and in vivo models of psoriasis, demonstrating its potential as a substitute for anti-IL-17A antibodies for treating psoriasis.http://www.sciencedirect.com/science/article/pii/S0753332224001379celastrolanti-IL-17A small molecule inhibitorautoimmune diseasepsoriasisautophagyinflammation |
| spellingShingle | Aeri Park Tae-Hwe Heo Celastrol regulates psoriatic inflammation and autophagy by targeting IL-17A Biomedicine & Pharmacotherapy celastrol anti-IL-17A small molecule inhibitor autoimmune disease psoriasis autophagy inflammation |
| title | Celastrol regulates psoriatic inflammation and autophagy by targeting IL-17A |
| title_full | Celastrol regulates psoriatic inflammation and autophagy by targeting IL-17A |
| title_fullStr | Celastrol regulates psoriatic inflammation and autophagy by targeting IL-17A |
| title_full_unstemmed | Celastrol regulates psoriatic inflammation and autophagy by targeting IL-17A |
| title_short | Celastrol regulates psoriatic inflammation and autophagy by targeting IL-17A |
| title_sort | celastrol regulates psoriatic inflammation and autophagy by targeting il 17a |
| topic | celastrol anti-IL-17A small molecule inhibitor autoimmune disease psoriasis autophagy inflammation |
| url | http://www.sciencedirect.com/science/article/pii/S0753332224001379 |
| work_keys_str_mv | AT aeripark celastrolregulatespsoriaticinflammationandautophagybytargetingil17a AT taehweheo celastrolregulatespsoriaticinflammationandautophagybytargetingil17a |